1. Fields of the Invention
The present invention relates to a chip with tri-layer electrodes and micro-cavity arrays for control of bioparticles and a manufacturing method thereof, especially to a chip that captures and releases cells/bioparticles into/from preset cavities by dielectrophoresis (DEP) force generated by electrodes, and a manufacturing method thereof. Cell trapping, cell release at the single-cell level and cell release at the cell population level are achieved by combinations of tri-layer electrodes and applications of AC (alternating current) electric field.
2. Descriptions of Related Art
Due to well development of MEMS (Micro Electro Mechanical Systems), studies regarding manipulation of a single cell have achieved great development. Among these studies, applications of dielectrophoresis force on biochips for cell positioning are most popular. The modules of cell biochips with the applications of dielectrophoresis have following functions: cell immobilization, transmission, separation, measurement, cell sorting, etc.
Publications on dielectrophoresis go as far back as 1978, by Herbert Pohl, England. Dielectrophoresis is defined as a phenomenon that when a cell is subjected to a non-uniform electric field such as non-uniform AC (alternating current) electric field, the cell surface is with induced charge due to dielectric property of the cell and a dipole moment with the same or opposite direction of the applied electric field is formed. Thus the cell is attracted to regions of stronger electric field due to positive dielectrophoresis force or concentrated to regions of weaker electric field by negative dielectrophoresis force. Therefore the electrode design allows the cell to be driven by the electric field gradient and fixed in a designed (preset) area.
Traditional techniques are divided into several groups as followings:
1. Refer to Taiwanese Pub. App. No. 1308131 (Prior art I), a bioparticle capture apparatus with three-dimensional microstructure is revealed, as shown in FIG. 12. The three-dimensional microstructure includes an upper layer, a lower layer and micro flow channels. The upper layer and the lower layer are respectively disposed with electrodes so as to generate dielectrophoresis (DEP) force for capturing bioparticles into preset wells. Except capture of bioparticles by DEP force, there is no other manipulation way of cells. The function of the device is limited.2. Refer to U.S. Pat. No. 6,692,952 (Prior art II), as shown from FIG. 13a to FIG. 13d, a cell analysis and sorting apparatus is revealed. The apparatus contains several cell locations (wells) that capture, hold and release the cells. An electric field trap formed by electrodes is used for capturing the cell and vapor bubbles eject the cell out of the well. The apparatus can also use to observe cell behavior, and sort cells.The electrodes are formed from gold and gaskets are made from PDMS (poly dimethyl siloxane). By applying current to electrodes, an electric field is produced to trap cells. After analysis, the vapor bubbles cause cell release. However, the longer the cell contacts with electrode, the greater the number of cell dead. Moreover, production of vapor bubbles may require higher or lower voltage/frequency. These conditions are not suitable for cell studies.
Among related studies, there is no single chip that attains both cell capture and programmable cell release at the single-cell level. Thus there is a need to develop a chip and a manufacturing method thereof that overcomes shortcomings of the techniques and chips available now and has more practical value.